Sandhu, Johnny S.

Background: The management of asymptomatic high-grade carotid stenosis remains challenging, particularly in identifying individuals at highest risk for hypoperfusion-related stroke. Impaired cerebrovascular reactivity (CVR) has emerged as a potential predictor of future cerebrovascular events. Objective: To perform a systematic review and meta-analysis to quantify the association between impaired CVR and the risk of ipsilateral ischemic stroke or TIA in patients with asymptomatic high-grade carotid stenosis/occlusion. Methods: A systematic literature search of PubMed, Embase and Scopus was conducted from inception till July 2025. Eligible studies included asymptomatic patients with ≥70% carotid stenosis or occlusion who underwent CVR assessment and reported ipsilateral ischemic stroke or TIA outcomes. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Forest plots were generated, and heterogeneity was assessed using the chi-square test and the I 2 statistic. Results: Six prospective observational studies including a total of 361 patients with asymptomatic high-grade carotid stenosis/occlusion (mean age 70.4 years; 73.6% male; 71.2% with hypertension; 28.6% with diabetes; 29.6% current or former smokers) were included in the analysis. Of these, 120 patients had impaired CVR and 241 had preserved CVR. Transcranial Doppler (TCD) was the most frequently used modality to assess CVR, with acetazolamide or CO 2 as the vasodilatory stimulus. Following CVR assessment, patients were monitored for a weighted mean follow-up of 26.2 months (range: 21.5 to 42.5 months). The incidence of ipsilateral ischemic stroke or TIA was 14.2% in patients with impaired CVR versus 2.1% in those with preserved CVR (RR 3.98; 95% CI 1.62–9.76; P = 0.003; Figure 1). When limited to ipsilateral ischemic stroke alone, the incidence was 21.4% in the impaired CVR group compared to 4.3% in the preserved CVR group (RR 3.35; 95% CI 1.54–7.25; P = 0.002; Figure 2). Conclusions: Impaired CVR is associated with a 3- to 4-fold increased risk of ipsilateral ischemic stroke or TIA in patients with high-grade carotid stenosis/occlusion. CVR assessment may help stratify risk and guide individualized management in this population.

Introduction: AI-driven software has been recommended as a means of triaging suspected large vessel occlusions (LVOs) on CT angiography (CTA), and different solutions are now commercially available. This study compared the performance of two software packages, Brainomix 360 Triage LVO and Rapid LVO, in prospective, real-world use. Methods: Consecutive patients scanned for suspected stroke at 3 comprehensive stroke centres from May to July 2024 (3 months) were included in the study. CTA, where available, was processed in real time by both Rapid and Brainomix software. Ground truth on vessel occlusion was ascertained using clinical review of electronic medical records. Occlusion location was coded as intracranial internal carotid artery terminus (ICA-T), middle cerebral artery (MCA) M1 or MCA M2. If more than one occlusion was observed, the most proximal of these was taken as the primary vessel affected. Results: There were 561 suspected stroke patients scanned during the study period across the three sites. Of these, CTA was sent for processing by both Rapid LVO and Brainomix 360 Triage LVO for 359 cases. Cases were excluded if no contrast was detected (n=17), leaving 342 cases (Table 1). Of these, proximal LVO (ICA-T or MCA M1) was confirmed in 14 cases and MCA M2 occlusions were present in 6 cases. Table 2 shows the LVO detection results for all cases from the two software packages. For both devices, sensitivity was higher when considering only proximal occlusions (ICA-T or M1). Performance was similar overall, but there was a trend towards differing sensitivity for more distal occlusions. As a composite measure, area under the curve (AUC) was higher for Brainomix than Rapid (Figure 1) but this difference was not significant. The positive predictive value (PPV) was low for both software packages due to the low incidence of LVO in the patient population. Conclusions: This study demonstrated consistent performance of two AI software devices, Brainomix 360 Triage LVO and Rapid LVO, for detection of LVO on CTA imaging, in prospective, real-world use. The low number of positive cases in the dataset (N=21) is a limitation of the study. There was a trend towards different performance for more distal vessel occlusion locations. Overall, the sensitivity observed in this dataset was in line with reports from previous retrospective studies for both software packages and underlines the importance of prospective evaluation to understand real-world performance.

Background: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) can be misdiagnosed as multiple sclerosis (MS). This study aims to contrast demographic, clinical, neuroimaging, and genetic features of CADASIL patients with vs. without prior MS misdiagnosis. Methods: We conducted a retrospective cohort study to compare genetically or histopathologically confirmed CADASIL patients with and without a prior MS misdiagnosis across Mayo Clinic. Patients were classified into high-, medium-, low-, or unknown-risk by location of NOTCH3 mutation. Disease severity was assessed using NOTCH3 Small-Vessel Disease (N3SVD) scale. Between-group comparisons used independent t-test for age, chi-square or Fisher’s exact test for categorical variables, and Mann–Whitney U test for quantitative variables. Within the misdiagnosed subgroup, neuroimaging changes between MS to CADASIL diagnosis were assessed using Wilcoxon signed-rank test for quantitative data and Stuart–Maxwell test for categorical data. Significance was set at p<0.05 (two-sided). Results: Among 107 patients (mean age 57.5±13.4 yrs) with CADASIL, 12 (11.2%) had a prior MS misdiagnosis (Table 1). Compared to patients without misdiagnosis (n=95), those misdiagnosed were younger, more frequently Asian, more likely to undergo lumbar puncture (83.3% vs 26.3%, p <0.001), and less likely to have had stroke (33.3% vs 65.3%, p =0.031). There were no significant differences in deep white matter hyperintensity scores or lacune counts. However, the misdiagnosed group had a higher median modified Rankin Scale ( p =0.008) and a different distribution of N3SVD stages ( p =0.017), with a higher proportion in stage 3A (33.3% vs 5.3%). There was no significant difference in genetic risk categories (Figure), but 5 of 12 misdiagnosed cases clustered in the medium risk EGFR 13, 13.5, and 14 domains. Among the misdiagnosed, 41.7% received MS-specific treatment during a median of 10.2 months (range 0.4–138.1) before diagnostic correction (Table 2). Over this period, there were no significant changes in DWMH score, lacune count, mRS, or N3SVD stage (all p >0.05). Conclusions: About one in nine CADASIL patients had a prior MS diagnosis. Atypical presentations in younger individuals without a clear stroke history may prompt consideration of MS over CADASIL, leading to diagnostic delays and unnecessary treatments. EGFR domain risk category did not correlate with misdiagnosis.